Various drug entities derived from plants and plant products have been disclosed over the years, for various therapeutic applications.
For example, Paraschos et al disclose preparation of a total mastic extract without polymer (TMEWP) by polar solvent extraction of crude mastic, removal of the insoluble polymer poly-β-myrcene therefrom, and separation of acidic and neutral fractions from TMEWP (Paraschos et al (2007) Antimicrob. Agents Chemother. 51(2):551-559).
International Patent Application Publication No. WO 2005/112967 is directed to the anticancer activity of mastic gum.
International Patent Application Publication No. WO 2010/100650 of some of the inventors of the present invention, is directed to therapeutic uses of mastic gum fractions.
International Patent Application Publication No. WO 2010/100651 of some of the inventors of the present invention, is directed to compositions of polymeric myrcene.
International Patent Application Publication NO. WO 2012/032523 of some of the inventors of the present invention, is directed to acidic compositions of mastic gum.
International Patent Application Publication No. WO 2005/094837 is directed to Use of masticadienonic acid as inhibitor of DNA polymerase-beta, used for treating cancers, tumors and neurodegenerative diseases.
Marner et al (1991) disclose identification of various triterpenoids from gum mastic of P. lentiscus (Marner et al (1991) Phytochemistry, 30, 3709-3712).
Giner-Larza et al (2002) disclose anti-inflammatory triterpenes from pistacia terebinthus galls (Planta Med (2002), 68, 311-315).
Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's Diseases (PD) and vascular dementia (VD) are adult onset, chronic, progressive and irreversible severely disabling diseases.
Vascular dementia (VD) is a subtype of dementia with a prevalence that is second only to that of Alzheimer's disease in westernized societies. VD causes many neuropsychiatric and physical problems, and represents a significant economic burden. Brain imaging has revealed obvious changes in the cerebral cortex and white matter, and these lesions are thought to be the core pathology for cognitive declines in patients with vascular dementia.
Alzheimer's disease (AD) is characterized by progressive mental and cognitive deterioration with consequent formation of amyloid plaques, neurofibrillary tangles, gliosis and neuronal loss. The disease occurs in both genetic and sporadic forms whose clinical course and pathological features are quite similar.
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease caused by a selective degeneration of dopaminergic neurons in the substantia nigra pars compacta of the brain; 80% of the neurons die of an unknown cause before the symptoms appear. Symptoms include intermittent tremor in the limbs, poor balance and difficulty in initiating movement. PD has a characteristic clinical syndrome of bradykinesia, tremor, rigidity, and postural instability. Degenerative parkinsonian disorders can be inherited or sporadic, but are all characterized by neuronal loss in selective populations of vulnerable neurons. The common denominator of all degenerative parkinsonian disorders is loss of dopaminergic neurons of the substantia nigra that project to the putamen (i.e., dopaminergic nigrostriatal pathway). Five main separate Parkinson-plus syndromes have been identified Multiple system atrophy (MSA), Progressive supranuclear palsy (PSP), Parkinsonism-dementia-amyotrophic lateral sclerosis complex, Corticobasal ganglionic degeneration (CBD) and Dementia with Lewy bodies (DLB). Additional Parkinson-plus syndromes include Pick's disease and olivopontocerebellar Atrophy (OPCA).
There remains an unmet need for safe, versatile and effective compounds and compositions, which may be obtained from plants by reproducible, highly efficient and cost-effective methods, for use in the treatment of Alzheimer's disease (AD), Parkinson's Diseases (PD) and/or vascular dementia (VD).